Transvascular stimulation of a vagus nerve via a catheter, for the purpose of heart rate reduction (parasympathetic drive), was first reported by Thompson et al. in 1998 [Thompson et al. “Bradycardia induced by intravascular versus direct stimulation of the vagus nerve”, Annals of Thoracic Surgery, 65 (3), 637-42, 1998]. A few years later, Hasdemir et al. [Hasdemir et al. “Endovascular stimulation of autonomic neural elements in the superior vena cava using a flexible loop catheter”, Japanese Heart Journal, 44 (3), 417-27, 2003] investigated the use of a flexible loop with multiple contacts in the superior vena cava (SVC). This work showed stimulation at anterior sites resulted in phrenic nerve stimulation, whereas posterior site stimulation affected sinus cycle length and atrioventricular conduction while avoiding phrenic nerve stimulation.
Transvascular stimulation of the phrenic nerves, on the other hand, dates back to the 1950s [Doris J. W. Escher et al. “Clinical control of respiration by transvenous phrenic pacing”, Trans. Amer. Soc. Artif. Int. Organs, Vol. XIV, 192-197, 1968]. WO2008/092246 A1 discloses a stimulation device with a single endovascular lead having multiple electrodes for stimulation of a vagus nerve and/or a phrenic nerve. The reference describes phrenic nerve stimulation to regulate breathing, and fine-tuning the positioning of the electrode array in the internal jugular vein (IJV) by observing the patient's breathing.
U.S. Pat. No. 8,433,412 B1 discloses a lead-electrode system for use with an Implantable Medical Device (IMD) configured to monitor and/or treat both cardiac and respiratory conditions. More particularly, versions of the invention relate to a lead-electrode configuration of a combination IMD that combines therapies such as cardiac pacing, respiratory sensing, phrenic nerve stimulation, defibrillation, and/or biventricular pacing, referred to as Cardiac Resynchronization Therapy (CRT). Stimulation and/or sensing leads may be placed in a small pericardiophrenic vein, a brachiocephalic vein, an azygos vein, a thoracic intercostal vein, or other thoracic vein that affords proximity to the phrenic nerve for stimulation. Respiration sensing may be performed via transthoracic impedance.
US 20140067032 A1 discloses an implantable medical system including an electrode-bearing lead that is implanted through the lumen wall of a blood vessel located adjacent to a target nerve, in particular a vagus nerve, with the lead including an anchor configured to secure the lead (and thereby the electrode) to tissue outside of the vessel near the target nerve.
U.S. Pat. No. 8,630,704 B2 discloses utilizing measurement of respiratory stability or instability during sleep or rest as a feedback to control stimulation of an autonomic neural target (e.g., vagus nerve stimulation).
Vagus nerve stimulation recently emerged as a potential progression-preventing and treatment option for CHF patients. Experimental data have demonstrated that stimulation of a vagus nerve at the cervical level is able to reverse ventricular remodeling of the failing heart. There is also evidence that increasing parasympathetic activity may stimulate the production of nitric oxide, and reduce the devastating inflammatory process involved in heart failure. Present vagus nerve stimulation devices for CHF involve an implanted nerve cuff electrode that connects via wires to an IPG in the patient's chest. A standard pacemaker sensing lead in the ventricle has been proposed in prior art for the purpose of synchronous delivery of vagus nerve stimulation pulses in the cardiac refractory period, although other prior art devices operate asynchronously to the cardiac cycle. Stimulation of both the right and left vagus nerves are disclosed in prior art for CHF treatment.
Implantations of nerve cuff electrodes require accessing and exposing the nerve. A drawback of such implantation is that the shape, size, thickness, orientation, flexibility, and associated leadout cables of the electrodes must carefully match the anatomical site to avoid nerve damage. A less invasive approach is preferred for cervical VNS, in particular one that can employ a lead implantable via well-established pacemaker-implantation techniques which avoid the need for additional physician training.
Another fact to consider is that almost half of the Congestive Heart Failure (CHF) patient population suffers from Central Sleep Apnea (CSA). Although CRT has become the standard device therapy for the treatment of NYHA class III or IV heart failure patients with left ventricular ejection fractions (LVEF)≤35% and QRS≥130 ms, only 7% of all eligible CHF patients receive the device (see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493802/), and approximately 30% of those who receive it are classified as non-responders (see http://circ.ahajournals.org/content/117/20/2608. abstract). Hence, a combination device as proposed by U.S. Pat. No. 8,433,412 B1 is not optimal for the treatment of CHF with CSA.
Central sleep apnea (CSA) can be managed/treated via phrenic nerve stimulation (PhrNS). However, these nerves are too fragile for nerve cuff electrodes. U.S. Pat. No. 8,433,412 B1 discloses an “implantable respiration lead” for transvascular stimulation of a phrenic nerve via installation in a pericardiophrenic vein, a brachiocephalic vein, an internal jugular vein (IJV), a superior intercostal vein, the superior vena cava (SVC), or other appropriate locations.
Transvascular stimulation of a nerve is appealing because the implantation of endovascular leads is well known by physicians dealing with CHF patients. The vascular system contains numerous locations therein which are in close proximity to vagus and phrenic nerves. However, chronically implanting a lead in a large, easily accessible vein as proposed by WO2008/092246 A1 requires a suitable anchoring solution not described in that reference. Furthermore, electrode structures as proposed by WO2008/092246 A1 may be prone to blood clot formation, and thus are preferably avoided for chronic implantation.